Method to make tube-in-tube balloon

ABSTRACT

A tube-in-tube assembled parison for preparation of an elongated medical device. The parison if formed by assembling in tube-in-tube fashion a first tube of orientable polymer material and a second tube formed of orientable polymer material disposed around the first tube, with an adhesive tie layer disposed between the first and second tubes. The tubes are brought into contact to form a unitary parison. The adhesive may allow movement between the polymer layers during balloon blowing. The first tube, or the second tube, or both, may have been longitudinally pre-stretched after formation thereof but before assembly of the parison.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/366,257, filed on Mar. 2, 2006, issuing as U.S. Pat. No. 8,043,673 onOct. 25, 2011, the entire contents of which are incorporated herein byreference.

FIELD OF THE INVENTION

The present invention pertains to an improved multilayer tube-in-tubeballoon parison and to medical device balloons formed therefrom.

BACKGROUND OF THE INVENTION

Balloons mounted on the distal ends of catheters are widely used inmedical treatment.

When medical device balloons are made by radial expansion of a tubularparison, there is typically a significant difference in the amount oforientation between the inner and outer layers of the balloon becausethe radial expansion of material on the outer side of the parison istypically significantly less than that of material at the inner side ofthe parison.

Multilayer balloons made from coextruded layers of different polymersare described in various patents including U.S. Pat. No. 5,270,086(Hamlin); U.S. Pat. No. 5,195,969 (J. Wang, et al.); U.S. Pat. No.5,290,306 (Trotta, et al); U.S. Pat. No. 5,879,369 (Ishida); and U.S.Pat. No. 5,797,877 (Hamilton et al).

As an alternative to a coextruded parison balloon, U.S. Pat. No.6,004,289 (Saab) describes medical balloons made by a successive processof extruding a parison, blowing a very thin wall balloon of inelasticmaterial such as high molecular weight PET, trimming away a portion ofthe balloon cone and the waist, replacing the trimmed balloon portion inthe mold, placing a second full length parison in the mold, blowing asecond thin-walled balloon of the same material inside the portion ofthe first balloon within the mold to produce a second balloon that hastwo layers in at least the body portion and a portion of the cone.Optionally the second balloon may be trimmed to remove at least itswaist and a portion of the cone not covered by the first balloon portionand the remnant replaced in the mold. Following placement of a thirdparison of the same material in the mold and blowing the third parisoninto the remnant of the second balloon, a third thin-walled balloon thathas staggered layers in the cone region, and three layers in the bodyregion is produced. This iterative process produces a balloon in whicheach layer is separately biaxially oriented with a relatively smallerdifference between the expansion of the inner and outer sides of theparison so that very high orientation prevails throughout the balloonbody. However the procedure is extremely tedious and labor intensive.

A less labor intensive tube-in-tube balloon process for formingmulti-layer balloons is described in U.S. Pat. No. 5,587,125(Roychowdhury). Polymer tubes of different, closely fitting, sizes areprepared, one in slipped over and drawn down on the other to produce atube-in-tube parison, and then the balloon is blown from that parison.

In U.S. Pat. No. 6,124,007 (L. Wang et al.), a tube-in-tube parison isprepared after at least one of the two polymer tubes has beenlongitudinally oriented by axial stretching. The layers may be the sameor different. Radial expansion of the tube-in-tube parison gives aballoon in which there is separate orientation of the two layers so thatsubstantial additional strength is provided to the laminate balloon.However, in some cases the balloon layers are poorly bonded anddelamination of the balloon may occur at burst. This is undesirable.

SUMMARY OF THE INVENTION

The invention is directed to a tube-in-tube parison in which an adhesivelayer is interposed between two tubes, and to novel balloons formedtherefrom. In one aspect the invention is directed to a tube-in-tubeassembled parison for preparation of an elongated medical device theparison comprising

a first tube of orientable polymer material,

a second tube formed of orientable polymer material disposed around thefirst tube, and

an adhesive tie layer disposed between the first and second tubes andcontacting the first and second tubes.

The two tubes may be formed of the same material or different materialand may be only part of a larger assembly of tubes used to make up theparison. The first tube, or the second tube, or both, may have beenlongitudinally pre-stretched after formation thereof but before assemblyof the parison. Post-stretching of the parison after assembly may beperformed before it is blown into a balloon.

A second aspect of the invention comprises a preferred method of makinga laminate balloon which includes the steps of

a) providing a first tube of a first polymer material, the first tubehaving an outer surface and an outer diameter;

b) providing a second tube of a second polymer material, the second tubehaving an inner surface and an inner diameter greater than the outerdiameter of the first tube;

c) inserting the first tube into the second tube segment;

d) bringing the second tube into direct annular contact with the firsttube to form a laminate parison; and

e) forming the laminate balloon by pressurizing the laminate parison ata temperature and pressure above ambient so as to expand the laminateparison structure,

wherein, prior to the inserting step c), a layer of adhesive is providedon the outer surface of the first tube or on the inner surface of thesecond tube, or both, the total adhesive thickness still allowingtube-in-tube assembly of the parison.

Another aspect of the invention is a medical balloon formed by radialexpansion of an assembled tubular parison of the invention.

DETAILED DESCRIPTION OF THE INVENTION

All published documents, including all US patent documents, mentionedanywhere in this application are hereby expressly incorporated herein byreference in their entirety. Any copending patent applications,mentioned anywhere in this application are also hereby expresslyincorporated herein by reference in their entirety.

The inventive balloon has better adhesion between the layers. Because ofthe adhesive tie layer, the layers are adhered to each other better andreinforce each other during inflation. The resulting balloon may have ahigher burst pressure than the balloon without adhesive layer.

Further, the invention also reduces or prevents layer separation duringballoon burst and afterwards as the device is withdrawn. With theballoons of the present invention there is a reduced chance that balloonfragments will escape into the body, thereby jeopardizing the safety ofthe patient.

The adhesive layer should be thin relative to the tubes employed in theparison formation. A parison thickness that provides 20% or less of theballoon wall thickness is desirable, preferably about 10% or less. Aminimum thickness that will be effective to maintain lamination at burstis preferred. In some cases a molecular monolayer may be effective. Fora typical catheter balloon of 1-10 mm diameter, the thickness of theadhesive may range from about 0.05 μm to about 2 μm.

Suitable adhesives may be formulated as hot-melt, emulsion, solvent orheat-curable adhesives. Relatively low melting hot-melt adhesives may beapplied to one of the tubes after formation of the tube or it may becoextruded as a thin layer on one of the two tubes during tubeformation. Emulsion adhesives have the advantage that they can beapplied and dried to tack-free condition with little effect on mostpolymer substrates of interest.

In some embodiments, heat activated adhesives that soften, melt or cureat blowing temp but are sufficiently tack-free at room temp to allow thetube-in-tube parison to be readily assembled are employed. Examples ofdocuments describing such adhesives include U.S. Pat. No. 4,427,744,U.S. Pat. No. 6,753,379, and U.S. Pat. No. 6,042,930. An antiblockingagent may be used to facilitate a tack-free surface prior to assembly.

Adhesives that are initially lubricious may also be used. Asolvent-borne pressure sensitive adhesive (PSA) can be applied to one ofthe tubes, and the parison assembled right before molding and while theadhesive is still insufficiently tacky to substantially interfere withassembly of the parison. The residual solvent can act as lubricantduring balloon molding. The material slides easily between the tubingsurfaces during balloon molding and expanding process (with the presenceof the solvent). The residual solvent will diffuse through thin wallpolymer film of the balloon wall and evaporate from the surface of theballoon during or shortly after the molding process is complete.

This invention also simplified manufacture process because two tubes areno longer required to be as tightly fit to each other during the parisonassembly process.

In another aspect the invention comprises a laminate balloon comprisingat least two layers of separately oriented thermoplastic polymermaterial, coextensive over at least the body portion of the balloon andwhich are joined by an adhesive tie-layer in the coextensive portion.

The two layers may be the same or different polymer materials. Theballoon may have an underlying layer made of a low compliant, highstrength polymer and an overlying layer of a softer and more flexiblepolymer material relative to the first polymer material. Such balloonshave good flexibility and surface softness, allowing catheters to trackdown into lesions relatively easily, good puncture resistance, goodabrasion resistance and good refold characteristics, all contributed bythe soft material top layer. Furthermore they also have a low complianceprofile with high burst strength.

The inventive balloon structures may have an additive burst pressure,meaning that they are stronger than a first single-layer referenceballoon corresponding to the underlying polymer layer. The additivestrength of the balloons of the invention is exhibited typically byburst strengths greater than the first reference balloon by at least50%, and in some embodiments at least 75%, of the strength of a secondsingle-layer reference balloon corresponding to the overlying relativelysoft flexible polymer layer. To obtain an additive strength it may benecessary to longitudinally orient both tubes before assembly of theparison. It may also be important to use an adhesive that allows forindependent sliding of the parison layers during balloon molding, forinstance by becoming active only when the adhesive temperature is nearor above the temperature at which the parison begins to expand duringthe balloon blowing process. In some cases, the adhesive may not becomeactivated until the balloon is heat set at a temperature higher than theblowing temperature.

The individual layers may be selected specifically for theircontribution to the overall properties of the balloon. These propertiesmay include burst strength, compliance, elasticity, abrasion and/orpinhole resistance, surface lubricity, surface softness or hardness, andbondability to materials to which the balloon is to be attached.

In some embodiments one or more layers the materials may be lowcompliant, high strength thermoplastic polymers. An example ispoly(ethylene terephthalate) (PET) of initial intrinsic viscosity of atleast 0.5, for instance, 0.7-1.3, as reported by the polymermanufacturer. Other high strength polyester materials, such aspoly(ethylene napthalenedicarboxylate) (PEN), polybutylenenaphthalate/phthalate copolyester such as Nouvelan®, sold by Teijin,Ltd., Japan, and polybutylene terephthalate (PBT); polyamides such asnylon 6, nylon 4/6, nylon 6/6, nylon 6/66, nylon 6/9, nylon 6/10, nylon6/12, nylon 11 and nylon 12, and aromatic/aliphatic polyamides;thermoplastic polyimides; liquid crystal polymers or blend compositionscontaining liquid crystal polymers and high strength engineeringthermoplastic polyurethanes such as Isoplast 301 sold by Dow ChemicalCo., are considered suitable alternative materials. Physical blends andcopolymers of such materials may also be used. A suitable thermoplasticpolyimide is described in U.S. Pat. No. 5,096,848 and is availablecommercially under the tradename Aurum® from Mitsui Toatsu Chemicals,Inc., of Tokyo, Japan. Examples of liquid crystal polymers include theproducts Vectra® from Hoechst Celanese, Rodrun® from Unitika, LX or HXseries polymers from DuPont and Xydar from Amoco.

Other polymers that a balloon layer may be formed from include ABS(acrylonitrile-butadiene-styrene) block copolymer, ABS/Nylon blends,ABS/polycarbonate blends and combinations thereof, styrene-acrylonitrileblock copolymers, other acrylonitrile copolymers, polyacrylamide,polyacrylates, polyacrylsulfones polyester/polycaprolactone blends,polyetheretherketone (PEEK), polyethersulfone (PES), polyetherimide(PEI), polyetherketone (PEK), polymethylpentene, polyphenylene ether,polyphenylene sulfide, polyolefins such as polyethylene andpolypropylene, olefin copolymers, such as ethylene-propylene copolymer,ethylene-vinyl acetate copolymers, ethylene-vinyl alcohol copolymers andpolyolefin ionomers, polyvinyl chloride, polycaprolactam,N-vinyl-pyrrolidone, polyurethanes and polysiloxanes.

Still other suitable polymers for use in forming one or more layers ofthe balloons of the invention are thermoplastic elastomers, especiallysegmented polyester/ether block copolymers, such as available under thetrademarks Arnitel® and Hytrel®; polyester-polyester block copolymerssuch as a polyester-polyester block copolymer having an aromaticpolyester as the hard segment and an aliphatic polyester as the softsegment sold by Toyobo, under the trade names Pelprene S6001, PelpreneS9001; flexible polyurethanes, such as sold under the trademarkPellethane®; and polyamide/ether block copolymers (PEBA), such as soldunder the Pebax® trademark. Particular examples include Arnitel EM 740,Pebax® 7233, 7033 and 6333. The block copolymers in some embodiments mayhave a hardness, Shore D scale, of at least 50 and a flexural modulus ofno more than about 150,000, in order to obtain good strength, complianceand softness characteristics. The Shore D hardness may be in the rangeof 50-75 and the flexural modulus may be in the range of 10,000-120,000.

In some embodiments the first and second tubes, independently, may beformed of a material selected from the group consisting of polyamideblock copolymers, polyester block copolymers, polyesters, polyamides,polyurethanes, polyurethane block copolymers, polyetheretherketones,polyolefins, polyolefin ionomers, liquid crystal polymers, acrylonitrilepolymers and copolymers, or a mixture or two or more thereof.

In accordance with the invention two different tubes are formed andprocessed into a parison. The tubes are extruded and, optionally,longitudinally stretched. The longitudinal stretching may be from 1× (nostretching) to about 2.5×, based on the original extruded tube length.This stretching process may be performed at ambient or highertemperature, for instance up to about 50° C. or even higher. At leastone of the tubes is longitudinally stretched before the parison isassembled. In some cases all of the tubes may be longitudinallystretched before they are assembled together to form the balloonparison. The tubes may be pressurized internally during stretching. Insome cases the internal pressure during longitudinal may be sufficientto maintain or expand the ID of the tube while the OD diminishes orstays the same.

If a hot melt adhesive is employed, the adhesive layer may be coextrudedonto one of the mating surfaces of the polymer tubes. In such case thetube after any stretching processing is assembled tube-in-tube mannerwith the adhesive layer at the interface.

A hot melt adhesive may also be applied to a tube by spray application.Curable liquid, solvent borne or dispersion adhesives may be applied byspraying, dip coating, painting, or the like. If a solvent basedadhesive is used it may be desirable to assemble the parison and blowthe balloon before the solvent has fully evaporated in order to allowthe individual layers of the parison to move independently duringblowing. Low vapor pressure solvents may be desirable. Residual solventstypically can readily removed form the much thinner membrane of theformed balloon by subjecting the balloon during a residence aging time,which may be accelerated by ventilation with dry air, or an inert gassuch as nitrogen and/or by subjecting the formed balloons to vacuum. Insome cases heating during the balloon blowing step may be sufficient todrive residual solvent from the balloon.

Heat activatable aqueous dispersion adhesives are known that may besuitably employed in the invention. Such an adhesive is typicallytack-free at ambient temperature, but softens and becomes adhesive whenheated. Such an adhesive should be activatable at or below the maximumtemperature encountered during the balloon blowing or a subsequentcrystallization step. Heat activated adhesives may also be applied assolvent based adhesives. Curable liquid adhesives that are initiated oraccelerated by heating may also be employed. Activation at too low atemperature, however, may not be desirable because the individual layersof the parison may not be able to move independently and prematurebonding at the tube interfaces may not allow for optimal orientation ofthe individual layers. In at least some cases the heat activationtemperature is above the glass transition temperature(s) of the polymermaterials of the adjacent tubes.

If a curable adhesive is used it may be one that is activated to cure byexposure to heat during molding and/or heat setting or it may be onethat is activated by mixing prior to application. Suitably it will curesufficiently slowly to allow the parison layer to remain mobile relativeto each other for at least a part of the time that the parison is beingradially expanded to form the balloon.

A moisture curing adhesive may be used, with the coated tube suitablykept isolated from moisture prior to assembly of the parison. Duringballoon blowing, or after the balloon is blown, exposure of the curableadhesive to moisture may be accomplished by diffusion through the thinwall of the laminate. The moisture source may be a liquid water bath, asteam source, or even extended exposure to ambient humidity.

A UV or ionizing radiation curing adhesive may also be used. Suitably anassembly containing such an adhesive is not exposed to a UV source priorto blowing the balloon. During balloon blowing, or after the balloon isblown, the adhesive may be irradiated with UV or ionizing radiationthrough the inner or outer layer of the laminate, or both, with afluence of radiation that is effective to initiate curing of theadhesive. Desirably the layer or layers through which the radiation istransmitted will have a low absorption of the relevant energy so thatthe radiation will penetrate to the adhesive layer and not negativelyimpact the layer polymer properties.

The adhesive, after curing, heat activation or solvent removal is onethat is effective to hold the adjacent polymer layers together at humanbody temperature. Consequently the laminate will have a reduced tendencyto fragment into unattached pieces if it is burst.

After the adhesive is in place, the parison is assembled by insertingthe inner into the outer tube and drawing or necking down the outer tubeby longitudinal stretching or thermal shrinking to bring it into directcontact with the inner tube. Two or more layers may be assembled in thisway. A mandrel may be used to support the inner tube as the outer tubeis drawn, necked or thermally shrunk onto the inner tube. Othertechniques for assembly of tube-in-tube parisons as described in U.S.Pat. No. 5,587,125 (Roychowdhury) or U.S. Pat. No. 6,124,007 (L. Wang etal.) can also be adapted for use in the present invention by use of anadhesive as described herein.

Before blowing the assembled parison may be further processed by anadditional longitudinal stretching step (post-stretching) if desired.Post-stretching may be particularly desireable in most cases where oneor more of the individual tubes making up the parison were not stretchedbefore assembly. By a combination of pre-assembly stretching of theindividual layers and post-stretching, the individual layers may have anaxial stretch ratio from 1.5 to 5.0×, and the ratio may be the same ordifferent between the layers. In some cases one or more layers may haveno longitudinal stretch ratio.

The parison may also be processed to thin regions of the parison thatwill become waist or cone and waist portions of the balloon. Knownprocesses for thinning include grinding and necking of such regions.

To form the balloon, a conventional balloon forming process is suitablyfollowed. In such a process the parison is typically heated at a moldtemperature of from about 90° C. to about 120° C., for instance 90-110°C. with sufficient pressure to blow the parison to the mold dimensions.This may be a multi step process. In some cases longitudinalpost-stretching may be performed concurrently with the blowing step. Theballoon may be quenched after it has been blow formed or furtherprocessed with a heat set or shrinking/annealing step.

For heat setting, in some embodiments the balloon is transferred to ahigher temperature bath, for instance 110°-150° C. with pressurizationmaintained, to enhance crystallization of the polymer of one or morelayers. Typically such a process reduces balloon compliance.Alternatively a heat set may be accomplished dynamically by employing amold temperature higher than the temperature needed to effectively blowthe balloon at the pressure employed. In such a process the blowing stepoccurs before the parison material reaches the mold temperature so thatholding the balloon in the mold until a time after its temperature hasstabilized provides the desired crystallization enhancement withouthaving to use a second molding apparatus or bath.

For a shrinking/annealing step the formed balloon may be held for a timeat lower pressure and/or a temperature than the temperature employed formolding, for instance a temperature in the range of 70° C.-100° C. andpressure of 0-50 psi to modify the compliance curve of the balloon in amanner that enhances compliance by lowering the diameter that theballoon obtains at a low nominal inflation pressure.

Following balloon formation it is suitably mounted on an elongatedcatheter or endoscopic device or the like, prior to sterilization of thecompleted medical device. For stent delivery a stent may be mounted overthe balloon mounted on a catheter before sterilization, or at the timeof use in a surgical sterile field.

Balloons of the invention may be prepared for use on medical devices invarious interventional medical specialties including cardiology,gastroenterology, pulmonary medicine, radiology, urology and vascularsurgery. Examples of useful applications include catheters used incoronary and vascular percutaneous transluminal angioplasty, cathetersused for ultrasound or laser imaging systems, catheters used to deliverand implant vascular prostheses, devices used to diagnose and treatgastrointestinal disorders, biliary interventional products used inendoscopic procedures in the gall bladder and bile ducts, and prostratedilatation catheters. Depending on the particular application, theballoons may be prepared with a wide range of inflated diameters,typically in the range of 1 mm to about 30 mm, and more typically 1.5 mmto about 20 mm, with typical lengths ranging from 5 mm to about 100 mm.

The above examples and disclosure are intended to be illustrative andnot exhaustive. These examples and description will suggest manyvariations and alternatives to one of ordinary skill in this art. Allthese alternatives and variations are intended to be included within thescope of the claims, where the term “comprising” means “including, butnot limited to.” Those familiar with the art may recognize otherequivalents to the specific embodiments described herein whichequivalents are also intended to be encompassed by the claims. Further,the particular features presented in the dependent claims can becombined with each other in other manners within the scope of theinvention such that the invention should be recognized as alsospecifically directed to other embodiments having any other possiblecombination of the features of the dependent claims. For instance, forpurposes of claim publication, any dependent claim which follows shouldbe taken as alternatively written in a multiple dependent form from allclaims which possess all antecedents referenced in such dependent claimif such multiple dependent format is an accepted format within thejurisdiction. In jurisdictions where multiple dependent claim formatsare restricted, the following dependent claims should each be also takenas alternatively written in each singly dependent claim format whichcreates a dependency from an antecedent-possessing claim other than thespecific claim listed in such dependent claim.

1. A medical balloon formed by radial expansion of an assembled tubularparison, the assembled tubular parison comprising: a first tube oforientable polymer material, a second tube formed of orientable polymermaterial disposed around the first tube, the first tube, or the secondtube, or both, having been longitudinally pre-stretched after formationthereof but before assembly of the parison, and an adhesive layerdisposed between the first and second tubes and contacting the first andsecond tubes, the adhesive is selected to allow relative movement of thematerials of the first and second tubes during heated radial expansionof the parison to form a balloon but which subsequent to balloonformation is effective to adhere the materials of the two layerstogether at human body temperature.
 2. The medical balloon of claim 1,the adhesive layer comprising a heat activatable aqueous dispersionadhesive, a heat activatable solvent based adhesive, a moisture curableadhesive, or a radiation curable adhesive the adhesive is unactivated oruncured during radial expansion of the parison.
 3. The medical balloonof claim 1 wherein the adhesive is a pressure sensitive adhesive.
 4. Themedical balloon of claim 3 wherein the adhesive is a heat activatableadhesive.
 5. The medical balloon of claim 3 wherein the adhesive is amoisture curable adhesive.
 6. The medical balloon of claim 3 wherein theadhesive is a UV or ionizing radiation curing adhesive.
 7. The medicalballoon of claim 1 wherein the adhesive is an emulsion adhesive.
 8. Themedical balloon of claim 1 wherein the first and second tubes,independently, are formed of a material selected from the groupconsisting of polyamide block copolymers, polyester block copolymers,polyesters, polyamides, polyurethanes, polyurethane block copolymers,polyetheretherketones, polyolefins, polyolefin ionomers, liquid crystalpolymers, acrylonitrile polymers and copolymers, or a mixture or two ormore thereof
 9. The medical balloon of claim 1 wherein the first andsecond tubes are formed of the same material.
 10. The medical balloon ofclaim 1 wherein the first and second tubes are formed of differentpolymer materials.
 11. The medical balloon of claim 1 wherein the firsttube comprises a low compliant, high strength polymer and the secondtube comprises a softer and more flexible polymer material relative tothe first polymer material.
 12. The medical balloon of claim 1 wherein,after formation of the assembly, the assembly has been longitudinallypost-stretched.
 13. The medical balloon of claim 1 wherein the adhesivelayer should provides 20% or less of the balloon wall thickness.
 14. Themedical balloon of claim 1 wherein the adhesive layer provides 10% orless of the balloon wall thickness.
 15. The medical balloon of claim 1wherein after formation of the medical balloon the medical balloon has adiameter of about 1-10 mm and the unimolecular thickness of the adhesivelayer is about 0.05 μm to about 2 μm.
 16. The medical balloon of claim 1wherein the adhesive layer after the balloon has been formed has aunimolecular thickness to about 2 μm.
 17. The medical balloon of claim 1wherein the first tube comprises a low compliant, high strength polymer.18. The medical balloon of claim 17 having an additive burst strength ofgreater by at least 50% than a medical balloon formed from the firstpolymer tube alone.
 19. The medical balloon of claim 1 wherein thesecond tube comprises a softer and more flexible polymer materialrelative to the first polymer material.
 20. The medical balloon of claim19 having an additive burst strength of great by at least 75% of amedical balloon formed from the second polymer tube alone.